A Study to Evaluate the Benefit and Safety of GSK2982772 in Moderate to Severe Psoriasis Participants

NCT04316585 | Completed Phase 1 Results DMC

• 1 other identifier: 208022
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 9

Brief Summary

Plaque psoriasis is a chronic relapsing inflammatory skin disease that is characterized by keratinocyte hyper-proliferation and epidermal hyperplasia. Standard treatment for psoriasis generally requires long-term use of topical therapies, psoralen and ultraviolet A (PUVA), ultraviolet B (UVB) and/or systemic immunosuppressant therapies to achieve and maintain adequate disease control. This is a multicenter, randomized, double-blind study conducted in participants with moderate to severe plaque psoriasis. The study will evaluate the efficacy, safety, pharmacokinetic and pharmacodynamics profile of 960 milligram (mg) GSK2982772 administered as a once daily modified release (MR) formulation. Participants will be randomized in a 2:1 ratio to receive either 960 mg GSK2982772 or placebo for 12 weeks. The duration of the study, including Screening and follow-up, will be approximately 21 weeks for each participant.

Conditions

Psoriasis

Keywords

Plaque Psoriasis; Modified Release; GSK2982772; Skin Biopsy

Outcome Measures

Primary Outcomes (1)

• Percentage (%) of Participants Who Achieved Greater Than or Equal (>=) to 75% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12

  The Psoriasis area severity index (PASI) is a standard tool for assessing the severity of psoriasis that considers the overall severity of erythema, induration, and scaling (each scored separately), and the extent of body surface area (BSA) affected with psoriasis. The 3 clinical signs are each graded on a 5-point scale (0=none to 4=severe) and the percent BSA affected is scored on a 7-point scale (0= 0% skin with psoriasis to 6= ≥ 90% skin with psoriasis). The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. The PASI is a composite scoring assessed by the investigator for the severity of lesions and the area affected into a single score with a range of 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Note: The 95% credible interval (CrI) was reported as a method of dispersion.

  Baseline and Week 12

Secondary Outcomes (11)

• Percentage of Participants Who Achieved >=50% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12

  Baseline and Week 12

• Percentage of Participants Who Achieved >=90% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12

  Baseline and Week 12

• Percentage of Participants Who Achieved >=100% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12

  Baseline and Week 12

• Change From Baseline in Psoriasis Area Severity Index (PASI) Scores at Week 12

  Baseline and Week 12

• Percentage of Participants Who Have a Static Investigator's Global Assessment (sIGA) Score of 0 or 1 at Week 12

  At Week 12

Study Arms (2)

Participants receiving GSK2982772 960 mg

EXPERIMENTAL

Participants will receive GSK2982772 960 mg oral tablets once daily for 12 weeks.

Drug: GSK2982772

Participants receiving placebo

PLACEBO COMPARATOR

Participants will receive GSK2982772 matching placebo oral tablets once daily for 12 weeks.

Drug: Placebo

Interventions

GSK2982772 DRUG

GSK2982772 will be available as MR tablet at a unit dose strength of 480 mg.

Participants receiving GSK2982772 960 mg

Placebo DRUG

GSK2982772 matching placebo tablets will be administered via the oral route.

Participants receiving placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants between 18 and 75 years of age inclusive, at the time of signing the informed consent.
• Diagnosis of plaque psoriasis for at least 6 months before Screening visit.
• Evidence of moderate to severe psoriasis, at Screening and Baseline before the first dose of study treatment, with: PASI score \>=12; Psoriasis plaques involving BSA \>=10 percent and sIGA\>=3.
• Candidate for systemic therapy or phototherapy (includes naïve or previously treated), in the opinion of the Investigator.
• Agrees to avoid any prolonged exposure to natural or artificial sources of ultraviolet (UV) radiation from 28 days before Day 1 until the follow-up visit, which may potentially impact the participant's psoriasis in the opinion of the Investigator.
• Body mass index (BMI) within the range of 18.5 to 40.0 kilogram (kg)/meter square (m\^2).
• Preclinical data has not identified risk of clinically relevant genotoxicity, however there is demonstrated/suspected risk of teratogenicity/fetotoxicity. Accordingly, the following contraceptive advice must be adhered to for male and female participants.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male participants are eligible to participate if they agree to the following during the intervention period and for at least 2 days (i.e. 5 terminal half-lives of GSK2982772) after the last dose of study intervention: Refrain from donating sperm plus either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed: Agree to use a male condom and will also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a WOCBP OR Is a WOCBP and using a contraceptive method that is highly effective preferably with low user dependency, during the intervention period and for at least 28 days (i.e. until resolution of potential drug interaction with combined hormonal contraceptives) after the last dose of study intervention. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (example an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.

You may not qualify if:

• Non-plaque forms of psoriasis (example erythrodermic, guttate, or pustular), in the opinion of the Investigator.
• Drug-induced psoriasis (example a new onset of psoriasis or an exacerbation from beta blockers, calcium channel blockers, lithium or anti-Tumor-Necrosis Factor \[TNF\] therapies).
• Diagnosis of psoriatic arthritis, uveitis, inflammatory bowel disease, or other immune-mediated conditions that are commonly associated with psoriasis for which a participant requires current systemic (oral, subcutaneous \[SC\], or intravenous \[IV\]) (including corticosteroids and biologics) immunosuppressant medical treatment.
• Current Suicidal Ideation Behavior (SIB) as measured using the Columbia Suicide Severity Rating Scale (C-SSRS) or a history of attempted suicide at Screening and before first dose of study treatment.
• Active infection, or a history of infections as follows: Hospitalization for treatment of infection within 60 days before Day 1; Current use of any suppressive therapy for a chronic infection (such as pneumocystis jirovecii, cytomegalovirus, herpes simplex virus, herpes zoster virus and atypical mycobacteria); Use of parenteral (IV or intramuscular) antibiotics (anti-bacterials, antivirals, antifungals, or anti-parasitic agents) within 60 days before Day 1; History of opportunistic infections within 1 year of Screening (example pneumocystis jirovecii, Cytomegalovirus \[CMV\] pneumonitis, aspergillosis). This does not include infections that may occur in immunocompetent individuals, such as fungal nail infections or vaginal candidiasis, unless it is of an unusual severity or recurrent nature; History of recurrent, chronic or other active infection that in the opinion of the Investigator may put the participant at unacceptable risk or interfere/confound the integrity of study data; Positive test for Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) at screening or interaction with known Coronovirus Disease 2019 (COVID19) positive contacts within 14 days prior to Day 1; History of latent or active Tuberculosis (TB), irrespective of treatment status; A positive diagnostic TB test at Screening defined as a positive QuantiFERON-TB Gold plus test.
• Current or history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Current or history of renal disease.
• Significant unstable or uncontrolled cardiovascular disease including uncontrolled hypertension.
• Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
• History of major organ transplant (example heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
• Planned surgical procedure that makes the participant unsuitable for the study, in the opinion of the Investigator.
• History of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell carcinoma) or carcinoma in situ of the uterine cervix that has been fully treated and shows no evidence of recurrence after at least 12 months following treatment.
• History of significant progressive neurologic disorders including, but not limited to, progressive Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's and dementia.
• History of a medical condition other than plaque psoriasis, or other considerations, which may confound interpretation of efficacy or safety study data, or put the participant at unacceptable risk, in the opinion of the Investigator.
• History of lack of primary response to anti-TNF biologic therapies (either approved or experimental) at approved doses (or at the doses received if experimental therapies) after at least 3 months of therapy.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (9)

GSK Investigational Site

Edmonton, Alberta, T5K 1X3, Canada

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1C3, Canada

Location

GSK Investigational Site

Surrey, British Columbia, V3R 6A7, Canada

Location

GSK Investigational Site

Truro, Nova Scotia, B2N 1L2, Canada

Location

GSK Investigational Site

London, Ontario, N6H 5L5, Canada

Location

GSK Investigational Site

Oakville, Ontario, L6J 7W5, Canada

Location

GSK Investigational Site

Peterborough, Ontario, K9J 5K2, Canada

Location

GSK Investigational Site

Québec, Quebec, G1N 4V3, Canada

Location

GSK Investigational Site

Lodz, 90-265, Poland

Location

MeSH Terms

Conditions

Psoriasis

Interventions

GSK2982772

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study where sponsor will be unblinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will randomized in ratio of 2:1 to receive either 960 mg GSK2982772 or placebo

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 20, 2020
• Study Start: September 28, 2020
• Primary Completion: September 13, 2021
• Study Completion: October 12, 2021
• Last Updated: March 18, 2024
• Results First Posted: March 18, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

PL (1); CA (8)